Design, synthesis, crystal structure, molecular docking studies of some diorganotin(IV) complexes derived from the piperonylic hydrazide Schiff base ligands as cytotoxic agents

Article abstract of DOI:10.1016/j.molstruc.2021.129992

Inspired by the role of organotin(IV) complexes in inhibition of cancer cell growth and interaction with different target proteins, we have synthesized a series of new organotin(IV) complexes of Schiff base ligands of benzylidene benzohydrazide analogues. The structural elucidation of compounds was done by spectroscopic studies showing tridentate nature (NOO) of Schiff base ligands having pentacoordinated geometry around the central tin metal. The X-ray crystallographic study of complex 9 (Me₂SnL²) revealed the distorted trigonal bipyramidal geometry (SnO₂NC₂). The cytotoxic activity of compounds was tested against human cancer cell lines A549, Hela, MCF7 and normal cell line L6 using MTT assay. Compound 12 (Ph₂SnL²), 14 (Et₂SnL³), 19 (Bu₂SnL⁴) was found most active against tested cell lines having IC₅₀ value 22.909–32.303 μM. Further, molecular docking study was performed for the active compounds 12, 14 and 20 at 3D space of enzymes Tyrosine kinase and EGFR kinase domain.

Full text of DOI:10.1016/j.molstruc.2021.129992

Journal of Molecular Structure 1232 (2021) 129992
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstr
Design, synthesis, crystal structure, molecular docking studies of some
diorganotin(IV) complexes derived from the piperonylic hydrazide
Schiff base ligands as cytotoxic agents
a,∗
a
a
b
b
c
Jai Devi , Jyoti Yadav , Kashmiri Lal , Nikhil Kumar , Avijit Kumar Paul , Deepak Kumar ,
e
d
Partha P. Dutta , Deepak Kumar Jindal
a
Department of Chemistry, Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science & Technology, Hisar, 125001, Haryana, India
Department of Chemistry, National Institute of Technology Kurukshetra, Kurukshetra, 136119, Haryana, India
School of Pharmaceutical Sciences, Shoolini University, Solan, 173212, India
b
c
d
e
Life Science Division, Institute of Advanced Studies in Science & Technology, Guwahati, Assam, 781035, India
Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science & Technology, Hisar, 125001, Haryana, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Inspired by the role of organotin(IV) complexes in inhibition of cancer cell growth and interaction with
different target proteins, we have synthesized a series of new organotin(IV) complexes of Schiff base
ligands of benzylidene benzohydrazide analogues. The structural elucidation of compounds was done by
spectroscopic studies showing tridentate nature (NOO) of Schiff base ligands having pentacoordinated
Received 10 October 2020
Revised 2 January 2021
Accepted 14 January 2021
Available online 4 February 2021
2
geometry around the central tin metal. The X-ray crystallographic study of complex 9 (Me2SnL ) revealed
Keywords:
the distorted trigonal bipyramidal geometry (SnO2NC2). The cytotoxic activity of compounds was tested
Schiff base: Piperonylic acid: Crystal:
Cytotoxic: Docking: Hydrazide
against human cancer cell lines A549, Hela, MCF7 and normal cell line L6 using MTT assay. Compound
12 (Ph SnL2), 14 (Et SnL3), 19 (Bu SnL4) was found most active against tested cell lines having IC value
2
2
2
50
22.909–32.303 μM. Further, molecular docking study was performed for the active compounds 12, 14
and 20 at 3D space of enzymes Tyrosine kinase and EGFR kinase domain.
©
2021 Elsevier B.V. All rights reserved.
1. Introduction
ordination number of tin metal as well as the groups which control
n+
the delivery of RnSn species [7–10].
Cancer is second leading cause of death after the cardiovas-
cular diseases worldwide. According to WHO report (2018), it is
estimated that 18.1 million new cases and 9.6 million deaths oc-
curred globally in 2018 [1]. Therefore, there is utmost need to de-
velop new cytotoxic drugs with high selectivity and low cytotox-
icity. Platinum based metallo drugs i.e. cisplatin was used in first
attempt for chemotherapy followed by carboplatin and oxaliplatin,
which have been used for the treatment of ovarian, lymphomas,
bladder, testicular, cervical and germ cell cancer [2]. However,
their incredible success is flawed by clinical limitations including
poor water solubility, intrinsic resistance problem and high toxic-
ity leading to severe side effects [3–5]. However, in an attempt to
reduce side effects/toxicity, some non-platinum drugs have gained
the attention and organotins have been identified as an effective
agent [6]. The anticancer activity of organotin(IV) is depended on
substituent (alkyl or aryl) group directly attached to tin metal, co-
Piperonylic acid is a naturally occurring heterocyclic compound
having methyldioxy as a functional group which is responsible for
its biological activity. It is nontoxic, water soluble compound which
improves the lipid metabolism, resist atherosclerotic proliferation,
enhances endothelial function, inhibit the growth of cancer cells,
prevent the microbial growth and also increase the immunity of
cells [11]. Hydrazides of piperonylic acid are used as precursors for
Schiff base ligands due to their structural flexibility, high stability
owing to formation of hydrogen bonding, conjugated system and
ease of complex formation. Schiff bases are important chelates not
only for synthetic manipulation but exhibit good inhibitory activ-
ity against the cancer cell lines and microbes. They are widely used
as frame work for complex formation. The presence of azomethine
bond in Schiff base ligands is responsible for the biological activ-
ities [12–17]. Specially, hydrazide Schiff bases having tridenticity
gives potential application in analytical and industrial field such as
pigments, dyes, catalyst in reduction of ketones, thionyl chloride,
henry reaction, polymerisation reaction, epoxidation of alkenes and
in DielsAlder reaction [18–24]. Hydrazide are reported to display
∗
Corresponding author.
E-mail address: jaidevi2005@gjust.org (J. Devi).
https://doi.org/10.1016/j.molstruc.2021.129992
0
022-2860/© 2021 Elsevier B.V. All rights reserved.

J. Devi, J. Yadav, K. Lal et al.
Journal of Molecular Structure 1232 (2021) 129992
2.4. Synthesis of Schiff base ligands (H L1–4)
enhanced biological activities when coordinated with tin metal and
also exhibit inhibition of cancer cell lines by different mechanis-
tic pathways [25–31]. Organotin(IV) complexes of piperonylic acid
showed good anticancer activity against brine shrimps, Agrobac-
terium tumefaciens and its phenyl, butyl, ethyl complexes and its
ruthenium complexes were found active against lung cancer cell
line which induces apoptosis by intrinsic pathway [32–35]. So, the
ligands play a key role in directing and transporting the complexes
to its target site and calculating its bioavailability. Thereby the
choice of a good ligand is very important in the synthesis of metal
complexes.
2
Piperonylic hydrazide (5 mmol, 0.900 g) was refluxed with
30 mL methanolic solution of salicylaldehyde/4-N,N diethyl
salicylaldehyde/5-nitro salicylaldehyde/3,5-dibromo salicylaldehyde
(5 mmol, 0.5 mL/0.96 g/0.835 g/1.395 g) with 2–3 drops of glacial
acetic acid. Green-yellow solid product was obtained which was
filtered, dried and recrystallised by using methanol.
N’-(2-hydroxybenzylidene)benzo[d][1,3]dioxole-5-
carbohydrazide, H2L1 [1]: -Yield: 92%, Yellow solid; M.p.: 190–
ο
−1
cm2 mol ) in DMF: 12.87, FT-IR (v,
−1
192 C, Conductivity: (ohm
cm 1): 3290 (O–-H, br), 1624 (C = N, m). 1H NMR [400 MHz,
−
In the view of aforementioned, it was planned to design and
synthesize some new diorganotin(IV) complexes from Schiff bases
of piperonylic acid hydrazides. Herein, we report the synthesis of
some new diorganotin(IV) complexes as cytotoxic agents. Further,
molecular docking against Tyrosine kinase and EGFR kinase was
done to study the target site for the compound 12, 14 and 20.
CDCl δ(ppm)]: 11.97 (s, 1H, C –OH), 11.32 (s, 1H, N–H), 8.61 (s,
3
2
1H,- N=C–H), 7.56–7.53 (2H, t, C - Ar-H, 3JH,H = 7.6 Hz), 7.48 (1H,
5,6
s, C ꢀ - Ar-H), 7.32–7.28 (1H, t, C ꢀ -Ar-H, 3JH,H = 7.6 Hz), 7.09–7.07
2
6
3
(1H, d, C ꢀ -Ar-H, JH,H = 8.16 Hz), 6.95 – 6.91 (2H, t, C
-Ar-H,
3,4
5
3
13
JH,H = 7.9 Hz), 6.14 (2H, s, -CH ): C NMR [100 MHz, DMSO,
2
δ(ppm)]: 163.28 (HO–C = N), 160.14 (HC=N), 148.31 (C–OH),141.16
(
(
C ), 139.48 (C ), 134.17 (C ), 130.47 (C ), 128.05(C ꢀ ), 124.22
1
2. Experimental
6
4
3, 5
1
C ꢀ ), 118.35 (C ꢀ ꢀ ), 113.15 (C ꢀ ), 108.10 (C 5ꢀ ), 42.24 (-CH ).MS:
6
3 , 4
2
2
+
+
m/z (M ) Cacld. for C15H N O : 284.07; found: 285.08 (M + H) .
2
.1. Materials
12
2
4
N’-(2–hydroxy-5-nitrobenzylidene)benzo[d][1,3]dioxole-
2
5
-carbohydrazide, H2L [2]:- Yield: 95%, Yellow solid; M.p.:
−1 −1
78–182 C, Conductivity: (ohm cm2 mol ) in DMF: 13.17, FT-IR
All chemicals and solvents were of reagent grade. Salicy-
ο
1
laldehyde derivatives, piperonylic acid and diorganotin dichloride
were obtained from Sigma-Aldrich Company. Solvents like hexane,
methanol, ethanol and tetrahydrofuran were used after drying with
standard procedures [36] and precautions were taken to maintain
glass apparatus, chemicals and synthesized compounds free from
any type of moisture.
v, cm 1): 3394 (O–H, br), 1642 (C = N, m). 1H NMR [400 MHz,
−
(
DMSO–d δ(ppm)]: 12.39 (s, 1H, C –OH), 12.15 (s, 1H, N–H), 8.72
6
2
s, 1H,- N = C–H), 8.60–8.59 (1H, d, C - Ar-H, 3JH,H = 2.48 Hz),
(
6
3
,4
8
.19–8.16 (1H, dd, C -Ar-H,
J
= 9.08, 2.88 Hz), 7.58–7.56 (1H,
4
H,H
d, C ꢀ - Ar-H, 3JH,H = 8.12 Hz), 7.50 (1H, s, C ꢀ -Ar-H), 7.13–7.11
6
2
(
1H, d, C3 - Ar-H, 3
J
= 9.08 Hz), 7.09–7.07 (1H, d, C ꢀ – Ar-H,
H,H
5
3JH,H = 8.12 Hz), 6.15 (2H, s, -CH ) : C NMR [100 MHz, DMSO,
13
2
2
.2. Instrumentation
δ(ppm)]: 173.49 (HO–C = N), 169.70 (HC=N), 164.20 (C–NO ),
2
1
50.22 (C–OH),138.79 (C ), 135.13 (C ), 133.02 (C ), 129.83 (C ꢀ ),
6
4
1
1
The melting points in degree celcius were determined using
1
23.19 (C ꢀ ), 120.37 (C ꢀ ꢀ ), 118.38 (C ), 112.17 (C2ꢀ, 5ꢀ ), 41.48 (-
6 3 , 4
+
4
electrical heating coil apparatus. FT-IR spectra of compounds were
recorded using Shimadzu IR affinity-I 8000 FT-IR spectrophotome-
CH ). MS: m/z (M ) Cacld. for C15H11 N O : 329.06; found: 330.33
2
3
6
+
(
M + H) .
ter at 4000–400 cm 1 using KBr pressed pellets. 1H, 13C and
119 Sn NMR spectra of synthesized compounds were recorded on
Bruker Avance II 400 MHz NMR spectrometer using DMSO–d6 and
−
N’-(4-(diethylamino)−2-hydroxybenzylidene)benzo[d][1,3]
3
dioxole-5-carbohydrazide, H L [3]:- Yield: 90%, greenish yellow
2
solid; M.p.: 178–180 C, Conductivity: (ohm cm2 mol ) in DMF:
ο
−1
−1
CDCl as solvent with tetramethylsilane and tetramethyltin as in-
2.78, FT-IR (v, cm ): 3475 (O–H, br), 1639 (C = N, m). 1H NMR
−1
3
1
ternal reference. The chemical shifts (δ) and coupling constants (J)
are given in ppm and Hz. Mass spectra was carried on SCIEX-QTOF
Mass spectrometer by using methanol as solvent at room temper-
ature. Molar conductance was calculated using conductivity bridge
type model- 306 Systronic in DMF solvent at room temperature.
Thermal gravimetric analysis (TGA) was measured using EXSTAR
[
400 MHz, DMSO–d δ(ppm)]: 11.11 (s, 1H, C –OH), 8.87 (s, 1H,
6 2
N–H), 8.30 (s, 1H,- N = C–H), 7.39–7.34 (2H, m, C ꢀ, 6ꢀ -Ar-H),
5
7
.03–7.01 (1H, d, C ꢀ -Ar-H, J = 8.64 Hz), 6.89–6.87 (1H, d, C -Ar-H,
2
3
3
J
= 1.20 Hz), 6.25–6.23 (2H, m, C
-Ar-H), 6.06 (2H, s, -CH ),
H,H
5,6
2
3
3
.42–3.36 (4H, q, -N-CH ,
J
= 7.28, 6.8 Hz), 1.22–1.19 (6H,
2
H,H
t, -N-CH , 3JH,H = 7.28, 6.8 Hz),: 13C NMR [100 MHz, DMSO–d ,
2
6
ο
TG/DTG 6300 at a heating rate of 10 C/min under high purity ni-
δ(ppm)]: 162.14 (HO–C = N), 158.87 (HC=N), 146.50 (C–OH),
trogen atmosphere.
1
43.33 (C ), 140.49 (C ), 136.60 (C ), 131.08(C ꢀ ), 126.28 (C ꢀ ),
4
6
1
1 6
The single-crystal data were collected on a Bruker D8 Advance
diffractometer at 296(2) K. The data were reduced using SAINT-
PLUS [37] and an empirical absorption correction was applied us-
ing the SADABS program [38]. The structure was solved and refined
using SHELXL97 [39] present in the WinGx suit of programs (Ver-
sion 1.63.04a) [40].
1
20.29 (C3ꢀ, 4ꢀ ), 118.39 (C ), 113.38 (C ꢀ ), 110.28 (C ꢀ ), 105.33 (C ),
2.58 (-CH ), 22.47 (N-Et-C), 66.22 (N-Et-C). MS: m/z (M ) Cacld.
5
2
5
3
+
4
2
+
for C19 H21N O : 355.15; found: 356.15 (M + H) .
3
4
N’-(3,5-dibromo-2-hydroxybenzylidene)benzo[d][1,3]dioxole-
-carbohydrazide, H2L4 [4]:- Yield: 94%, yellow solid; M.p.:
5
75–182 C, Conductivity: (ohm−1 cm2 mol−1) in DMF: 13.65, FT-IR
ο
1
v, cm 1): 3428 (O–H, br), 1616 (C = N, m). 1H NMR [400 MHz,
−
(
2
.3. Synthesis of piperonylic hydrazide precursor
DMSO–d δ(ppm)]: 13.53 (s, 1H, C –OH), 12.33 (s, 1H, N–H), 9.24
6 2
(
s, 1H,- N = C–H), 8.62–8.61 (1H, d, C - Ar-H, J = 2.48 Hz),
6
3
,4
In the methanolic solution of piperonylic acid, 1 mL of con-
8.43–8.40 (1H, dd, C -Ar-H,
J
= 9.08, 2.88 Hz), 7.45–7.44 (1H,
4
H,H
d, C ꢀ - Ar-H, 3JH,H = 8.12 Hz), 7.39 (1H, s, C ꢀ -Ar-H), 7.12–7.11
centrated H SO was added and refluxed for 6 h with dean stark
2
4
ο
6
2
3
13
apparatus at 40 C temperature to prevent the reversible reaction.
After refluxing the solution, ester formed was extracted by us-
ing the dichlomethane as solvent. Ester formed was dissolved in
methanol and then added 10 mL of hydrazine hydrate and further
refluxed for 2 h leading to the formation of piperonylic hydrazide.
The progress of the reaction was checked by thin layer chromatog-
raphy.
(1H, d, C ꢀ – Ar-H,
J
= 8.12 Hz), 6.21 (2H, s, -CH ) C NMR
5
H,H
2
[100 MHz, DMSO – d , δ(ppm)]: 173.92 (HO–C = N), 170.20
6
(HC=N), 162.18 (C -Br), 150.03 (C–OH),140.21 (C ), 139.89 (C ),
3
6
4
133.72 (C ), 131.27 (C ꢀ ), 130.79 (C ꢀ ), 126.48 (C ꢀ ꢀ ), 122.70
1
1
6
3 , 4
+
(C ꢀ ꢀ ), 43.89 (-CH ),.MS: m/z (M ) Cacld. for C15H10Br N O :
2
, 5
2
2
2
4
+
439.90; found: 440.90 (M + H) .
2

J. Devi, J. Yadav, K. Lal et al.
Journal of Molecular Structure 1232 (2021) 129992
Ar-H, 3JH,H = 8.16 Hz), 6.82–6.78 (m, 1H, C ), 6.07 (s, 1H, -CH ).
2
.5. Synthesis of diorganotin(IV) complexes (5–20)
3
2
13
C NMR [100 MHz, CDCl . δ(ppm)]: 171.18 (HO–C = N), 165.70
3
Schiff base ligand H L1 (0.28 g, 1 mmol) was mixed with tri-
2
(HC=N), 153.14 (C–OH),148.02 (C ), 141.14, 139.18, 137. 09 (C
6
),
3, 4, 5
ethylamine (0.278 mL, 2 mmol) and stirred in dried tetrahydrofu-
ran (20 mL) for 30 min. Dimethyltin dichloride (2.19 g, 1 mmol)
was added and resulting mixture was refluxed for 6–8 h. The
133.04 (C ), 131.08(C ꢀ ), 125.09 (Sn-C), 123.67 (Sn-C), 120.34 (C ꢀ ),
1
1
6
1
19
118.89 (C3ꢀ, 4ꢀ ), 114.16 (C ꢀ ), 110.28 (C 5ꢀ ), 44.06 (-CH ).
Sn NMR
2
2
+
[149.21 MHz, CDCl , δ(ppm)]: −329.89. MS: m/z (M ) Cacld. for
3
+
Et NHCl salt formed was filtered and solvent was evaporated on
C
H
27 20
N O Sn: 555.16; found: 556.17 (M + H) .
3
2
4
2
ο
rotary evaporator under reduced pressure to get red colored prod-
uct. The product was recrystallized from dry hexane and resulting
compound was dried. The other tin complexes were synthesized
Me SnL [9]: Yield: 71%, yellow solid; M.p.: 150–153 C, Con-
2
ductivity: (ohm 1 cm2 mol ) in DMF: 14, FT-IR (v, cm ): 1647
−
−1
−1
(C = N, m), 443 (Sn-N), 667 (Sn-O). 1H NMR [400 MHz, CDCl3,
2
3
4
by reacting the suitable amount of ligands, H L / H L / H L with
δ(ppm)]: 8.78 (s, 1H, -N = C–H), 8.21–8.17 (m, 2H, C4,6-Ar-H), 7.71–
2
2
2
3
appropriate amount of R SnCl in 1:1 molar ratio according to the
7.68 (d, 1H, C ꢀ -Ar-H,
J
H,H
= 8.12 Hz), 7.56 (s, 1H, C ꢀ -Ar-H), 6.88–
2
2
6
2
6.86 (d, 1H, C ꢀ -Ar-H, 3JH,H = 8.16 Hz), 6.79–6.77 (d, 1H, C -Ar-H,
above described procedure.
5
3
1
ο
3
13
Me SnL [5]: Yield: 65%, yellow solid; M.p.: 150–155 C, Con-
JH,H = 9.12 Hz), 6.05 (s, 2H, -CH ), 0.91 (s, 6H, Me). C NMR
2
2
−
1
cm2 mol ) in DMF: 12.77, FT-IR (v, cm ):
−1
−1
ductivity: (ohm
[100 MHz, CDCl . δ(ppm)]: 177.21 (HO–C = N), 172.22 (HC=N),
3
1
647 (C = N, m), 482 (Sn-N), 661 (Sn-O). 1H NMR [400 MHz,
167.45 (C–NO ), 154.22 (C–OH),141.18 (C ), 139.78 (C ), 135.22 (C ),
2
6
4
1
CDCl , δ(ppm)]: 8.74 (s, 1H, -N
C ꢀ -Ar-H, 3,4JH,H
=
C–H), 7.69–7.66 (dd, 1H,
131.18 (C ꢀ ), 130.09 (C ꢀ ), 127.89 (C ꢀ ꢀ ), 125.14 (C ), 122.21 (C ꢀ ꢀ ),
1 6 3 , 4 2 , 5
3
4
=
1.56, 8.16 Hz), 7.57–7.56 (d, 1H, C2ꢀ -Ar
-
119
6
44.20 (-CH2), 9.02 (Me).
Sn NMR [149.21 MHz, CDCl3, δ(ppm)]:
3
H, JH,H = 1.56 Hz), 7.37–7.33 (m, 1H, C -Ar-H), 7.21–7.19 (dd,
+
6
−156.23. MS: m/z (M ) Cacld. for C17 H15N O Sn: 476.02; found:
3
6
3
,4
1
H, C -Ar-H,
J
= 1.72, 7.8 Hz), 6.87–6.85 (d, 1H, C ꢀ -Ar-
4,5
+
3
H,H
5
477.02 (M + H) .
H, 3JH,H = 8.16 Hz), 6.80–6.74 (m, 2H, C -Ar-H), 6.04 (s, 2H,
2
ο
Et SnL [10]: Yield: 64%, yellow solid; M.p.: 156–160 C, Con-
2
13
-
CH ), 0.84 (s, 6H, Me).
C NMR [100 MHz, CDCl . δ(ppm)]:
−1 cm2 mol−1) in DMF: 13.72, FT-IR (v, cm−1):
2
3
ductivity: (ohm
)
(
]: 171.02 (HO–C
=
N), 165.58 (HC=N), 150.04 (C–OH),151.72
645 (C = N, m), 447 (Sn-N), 661 (Sn-O). 1H NMR [400 MHz,
1
C ), 149.04, 144.66 (C
6
), 140.39 (C ), 137.79(C ꢀ ), 133.47 (C ꢀ ),
3, 4, 5
1
1
6
CDCl , δ(ppm)]: 8.75 (s, 1H, -N = C–H), 8.22–8.19 (m, 2H, C4,6-
3
1
119
30.50 (C3ꢀ ꢀ ), 128.70 (C ꢀ ), 122.48 (C 5ꢀ ), 44.59 (-CH ), 9.83 (Me).
3
, 4
2
2
Ar-H), 7.70–7.67 (d, 1H, C ꢀ -Ar-H, JH,H = 8.12 Hz), 7.56 (s, 1H,
6
+
3
Sn NMR [149.21 MHz, CDCl , δ(ppm)]: −150.64. MS: m/z (M )
C ꢀ -Ar-H), 6.84–6.86 (d, 1H, C ꢀ -Ar-H,
J
= 8.16 Hz), 6.79–6.77
3
H,H
2
5
3
Cacld. for C17
1
H
N O Sn: 431.04; found: 432.05 (M + H)
(d, 1H, C -Ar-H, JH,H = 9.12 Hz), 6.05 (s, 2H, -CH ), 1.40–1.37
16
2
4
3
2
ο
(t, 6H, 3JH,H = 7.34 Hz), 0.93–0.91 (q, 4H, Me,
3
Et SnL [6]: Yield: 60%, yellow solid; M.p.: 150–155 C, Con-
J
= 8.35 Hz).
2
H,H
ductivity: (ohm 1 cm2 mol ) in DMF: 13.56, FT-IR (v, cm ):
−
−1
−1
13
C NMR [100 MHz, CDCl . δ(ppm)]: 176.14 (HO–C = N), 171.89
3
1
607 (C = N, m), 467 (Sn-N), 651 (Sn-O). 1H NMR [400 MHz,
(HC=N), 163.22 (C–NO ), 155.09 (C–OH),140.32 (C ), 136.12 (C ),
2
6
4
CDCl , δ(ppm)]: 8.73 (s, 1H, -N
=
C–H), 7.68–7.65 (dd, 1H,
133.45 (C ), 131.11 (C ꢀ ), 129.06 (C ꢀ ), 124.18 (C ꢀ ꢀ ), 120.14 (C ),
3
1
4
1
6
3 , 4
C ꢀ -Ar-H,
J
=
1.56, 8.16 Hz), 7.53–7.52 (d, 1H, C2ꢀ -Ar -H,
119
6
118.67 (C2ꢀ, 5ꢀ ), 46.01 (-CH2), 41.07 (Et-C), 9.78 (Et-C).
Sn NMR
4
JH,H
=
1.56 Hz), 7.41–7.39 (m, 1H, C6-Ar-H), 7.30–7.28 (dd,
+
[149.21 MHz, CDCl , δ(ppm)]: −155.67. MS: m/z (M ) Cacld. for
3
1
H, C -Ar-H, 3,4JH,H = 1.72, 7.8 Hz), 7.04–7.02 (d, 1H, C ꢀ -Ar-H,
4,5
+
3
5
C
H
N O Sn: 504.08; found: 505.10 (M + H) .
19
19
3
6
2
3JH,H = 8.16 Hz), 6.91–6.87 (m, 2H, C -Ar-H), 6.09 (s, 2H, -
ο
Bu SnL [11]: Yield: 65%, yellow solid; M.p.: 165–167 C, Con-
2
3
CH ), 1.34–1.30 (t, 6H, -CH ,
J
H,H
= 7.32 Hz), 0.91–0.88 (q, 4H,
ductivity: (ohm cm2 mol ) in DMF: 14.07, FT-IR (v, cm ): 1646
(C = N, m), 446 (Sn-N), 670 (Sn-O). 1H NMR [400 MHz, CDCl3,
δ(ppm)]: 8.77 (s, 1H, -N = C–H), 8.21–8.16 (m, 2H, C4,6-Ar-H), 7.72–
−1
−1
−1
2
3
13
-
CH2, 3JH,H = 8.34 Hz).
C NMR [100 MHz, CDCl . δ(ppm)]:
3
1
71.67 (HO–C = N), 165.55 (HC=N), 153.14 (C–OH),151.18 (C ),
6
1
48.47, 145.44 (C3
), 137.89 (C ), 132.45(C ꢀ ), 127.20 (C ꢀ ), 125.18
7.00 (m,1H, C ꢀ -Ar-H), 7.576–7.573 (d, 1H, C ꢀ -Ar-H, 4J
, 4, 5
1
1
6
= 1.56 Hz
6
2
H,H
(
C ꢀ ꢀ ), 122.10 (C ꢀ ), 114.75 (C ꢀ ), 45.07 (-CH ), 26.54 (Et-C), 10.14
3
3
, 4
2
5
2
), 6.89–6.87 (d, 1H, C ꢀ -Ar-H, JH,H = 8.16 Hz), 6.79–6.77 (d, 1H,
5
Et-C). 1 Sn NMR [149.21 MHz, CDCl , δ(ppm)]: −153.14. MS: m/z
19
C3-Ar-H, 3JH,H = 9.12 Hz), 6.06 (s, 2H, -CH ), 1.45–1.35 (m, 12H),
(
(
3
2
+
+
0.91–0.88 (t, 6H, 3
13
M ) Cacld. for C
1
H
N O Sn: 459.08; found: 459.10 (M + H) .
J
= 7.32 Hz). C NMR [100 MHz, CDCl .
19
20
2
4
H,H
3
ο
Bu SnL [7]: Yield: 67%, yellow solid; M.p.: 152–157 C, Con-
δ(ppm)]: 171.90 (HOC=N), 169.89 (HC=N), 158.81 (C–NO ), 150.54
2
2
ductivity: (ohm 1 cm2 mol
−
−1
) in DMF: 14, FT-IR (v, cm ):
−1
(C–OH), 147.72 (C ), 137.91 (C ), 130.77 (C ), 129.42 (C ꢀ ), 126.76
6
4
1
1
1
606 (C = N, m), 487 (Sn-N), 608 (Sn-O). 1H NMR [400 MHz,
(C ꢀ ), 123.04–122.20 (C ꢀ ꢀ ), 108.06 (C ꢀ ), 107.99 (C ), 101.56(C ꢀ ),
6 3 , 4 2 5
4
CDCl , δ(ppm)]: 8.75 (s, 1H, -N
C ꢀ -Ar-H, 3,4JH,H
=
C–H), 7.59–7.61 (dd, 1H,
45.81(-CH ), 26.73 (Bu-C), 26.42 (Bu-C), 22.68 (Bu-C), 13.54 (Bu-C).
2
3
119
+
=
1.56, 8.16 Hz), 7.59–7.57 (d, 1H, C2ꢀ -Ar
-
Sn NMR [149.21 MHz, CDCl , δ(ppm)]: −227.09. MS: m/z (M )
6
3
3
+
H, JH,H = 1.56 Hz), 7.29–7.25 (m, 1H, C -Ar-H), 7.15–7.13 (dd,
Cacld. for C
H
23 28
N O Sn: 560.18; found: 561.16 (M + H) .
6
3
6
3
,4
2
ο
1
H, C -Ar-H,
J
= 1.72, 7.8 Hz), 7.03–7.00 (d, 1H, C ꢀ -Ar-H,
4,5
Ph SnL [12]: Yield: 65%, yellow solid; M.p.: 165–167 C, Con-
2
3
H,H
5
3JH,H = 8.16 Hz), 6.94–6.90 (m, 2H, C -Ar-H), 6.01 (s, 2H, -
cm2 mol ) in DMF: 14.78, FT-IR (v, cm ):
−1 −1 −1
ductivity: (ohm
1646 (C = N, m), 450 (Sn-N), 636 (Sn-O). 1H NMR [400 MHz,
CH ), 1.61–1.59 (m, 4H), 1.32–1.29 (m, 8H), 0.83–0.80 (t, 6H, Me,
2
3JH,H = 7.32 Hz).
13
C NMR [100 MHz, CDCl . δ(ppm)]: 170.30
3
CDCl , δ(ppm)]: 8.78 (s, 1H, -N = C–H), 8.24–8.23 (m, 2H, C4,6-
3
4
(
HO–C = N), 165.02 (HC=N), 155.18 (C–OH),150.56 (C ), 143.04,
Ar-H), 7.91–7.90 (d, 1H, C -Ar-H,
J
H,H
= 3.56 Hz), 7.85–7.82 (m,
4
6
3
1
42.57, 137.21 (C3
), 130.48 (C ), 128.74(C ꢀ ), 120.34 (C ꢀ ), 117.23
2H, C5ꢀ,6ꢀ -Ar-H), 7.73–7.72 (d, 1H, C ꢀ -Ar-H,
J
H,H
= 1.6 Hz), 7.64–
, 4, 5
1
1
6
2
(
(
C ꢀ ꢀ ), 112.63 (C ꢀ ), 106.75 (C 5ꢀ ), 45.00 (-CH ). 37.18 (Bu-C), 35.14
7.62 (m, 2H, Sn-Ar-H), 7.47–7.45 (m, 4H, Sn-Ar-H), 7.34–7.32 (m,
2H, Sn-Ar-H), 6.95–6.92 (m, 2H, Sn-Ar-H), 6.09 (s, 2H, -CH2). 13
3
, 4
2
2
Bu-C), 26.19 (Bu-C), 12.89 (Bu-C). 119 Sn NMR [149.21 MHz, CDCl3,
C
+
δ(ppm)]: −212.14. MS: m/z (M ) Cacld. for C23H28N O Sn: 515.18;
NMR [100 MHz, CDCl3. δ(ppm)]: 178.19 (HOC=N), 170.74 (HC=N),
2
4
+
found: 516.16 (M + H) .
160.15 (C–NO2), 153.13 (C–OH),136.02 (C6), 134.85 (C4), 131.02 (C1),
1
ο
Ph SnL [8]: Yield: 70%, yellow solid; M.p.: 164–167 C, Conduc-
tivity: (ohm 1 cm2 mol ) in DMF: 13.04, FT-IR (v, cm ): 1649
130.83, 129.86, 129.64 (C ꢀ ), 129.17 (Sn-C), 128.62 (Sn-C), 128.59
2
1
−
−1
−1
119
(C ꢀ ), 123.33 (C3ꢀ, 4ꢀ ), 122.69 (C4), 122.16 (C2ꢀ, 5ꢀ ), 45.81 (-CH2).
Sn
6
C = N, m), 503 (Sn-N), 637 (Sn-O). 1H NMR [400 MHz, CDCl3,
+
(
NMR [149.21 MHz, CDCl3, δ(ppm)]: −334.78.MS: m/z (M ) Cacld.
+
δ(ppm)]: 8.74 (s, 1H, -N = C–H), 7.90–7.85 (m, 4H, Sn-Ar-H), 7.72–
for C27H19 N3O6Sn: 600.16; found: 601.03 (M + H) .
3
7
.68 (m, 1H, Sn-Ar-H), 7.46–7.39 (m, 7H, C4,5, Sn-Ar-H), 7.23–7.20
Me2SnL [13]: Yield: 70%, yellow green solid; M.p.: 153–
dd, 1H, C -Ar-H, 3,4JH,H = 1.64, 7.82 Hz), 7.13–7.11 (d, 1H, C ꢀ -Ar-H,
ο
cm2 mol ) in DMF: 13.55, FT-IR
−1 −1
(
157 C, Conductivity: (ohm
6
6
3JH,H = 8.28 Hz)), 7.02–7.00 (s, 1H, C ꢀ -Ar-H), 6.94–6.92 (d, 1H, C ꢀ -
(v, cm−1): 1649 (C = N, m), 408 (Sn-N), 630 (Sn-O). 1H NMR
2
5
3

J. Devi, J. Yadav, K. Lal et al.
Journal of Molecular Structure 1232 (2021) 129992
4JH,H = 2.48 Hz), 7.69–7.67 (dd, 1H, C ꢀ -Ar-H, 3,4JH,H = 1.6, 8.16 Hz),
[
400 MHz, CDCl , δ(ppm)]: 8.49 (s, 1H, -N = C–H), 7.62–7.59
3
2
4
(
dd, 1H, C ꢀ -Ar-H, J = 1.48, 8.12 Hz), 7.52–7.519 (d, 1H, C ꢀ -Ar-
7.56–7.55 (d, 1H, C ꢀ -Ar-H,
J
= 1.36 Hz), 7.26–7.25 (d, 1H, C -
6
2
6
H,H
4
4
3
Ar-H, 4JH,H = 2.44 Hz), 6.87–6.85 (d, 1H, C ꢀ -Ar-H,
3
H,
J
= 1.4 Hz), 6.99–6.97 (d, 1H, C -Ar-H,
J
= 8.92 Hz),
J
H,H
= 8.2 Hz),
H,H
6
H,H
3
3
13
6
.84–6.82 (d, 1H, C ꢀ -Ar-H,
J
= 8.16 Hz), 6.18–6.16 (dd, 1H, C -
6.04 (s, 2H, -CH ), 0.89 (s, 6H, Me). C NMR [100 MHz, CDCl .
2 3
5
H,H
5
Ar-H, 3 JH,H = 2.36, 8.92 Hz), 6.00 (s, 1H, -CH ), 5.968–5.962 (d,
,4
2
δ(ppm)]: 179 (HO–C = N), 174.30 (HC=N), 164.05 (C -Br), 154.22
3
1
H, C -Ar-H, 4
J
= 2.24 Hz), 3.42–3.36 (q, 4H,
H,H
3
J
= 14.12 Hz),
(C–OH),141.18 (C ), 139.78 (C ), 135.22 (C ), 131.18 (C ꢀ ), 130.09
3
H,H
H,H
6
4
1
1
13
119
1
.22–1.19 (t, 6H, -CH3, 3
J
= 7.04 Hz), 0.79 (s, 6H, Me). C NMR
(C ꢀ ), 127.89 (C3ꢀ, 4ꢀ ), 122.21 (C ꢀ ꢀ ), 44.20 (-CH ), 9.01 (Me).
Sn
6
2 , 5
2
+
[
100 MHz, CDCl . δ(ppm)]: )]: 167.23 (HO–C = N), 161.07 (HC=N),
NMR [149.21 MHz, CDCl , δ(ppm)]: −157. MS: m/z (M ) Cacld. for
3
3
+
1
48.20 (C–OH), 146.59 (C ), 143.16 (C ), 139.89 (C ), 135.14(C ꢀ ),
C
H
17 14
Br N O Sn: 588.82; found: 589.82 (M + H) .
4
6
1
1
2
2
4
4
ο
1
29.63 (C ꢀ ), 122.14 (C ꢀ ꢀ ), 121.68 (C ), 119.76 (C ꢀ ), 115.13 (C 5ꢀ ),
13.67 (C ), 47.08 (-CH ), 24.79 (N-Et-C), 70.09 (N-Et-C), 8.70 (Me).
Et SnL [18]: Yield: 73%, yellow solid; M.p.: 153–157 C, Con-
2
6
3 , 4
5
2
ductivity: (ohm 1 cm2 mol ) in DMF: 13, FT-IR (v, cm ): 1667
−
−1
−1
1
3 2
1
19
+
1
Sn NMR [149.21 MHz, CDCl , δ(ppm)]: −150.14.MS: m/z (M )
(C = N, m), 465 (Sn-N), 663 (Sn-O). H NMR [400 MHz, CDCl ,
3
3
Cacld. for C21
3
H
N O Sn: 503.15; found: 504.16 (M + H).
δ(ppm)]: 8.65 (s, 1H, -N = C–H), 7.79 - 7.78 (d, 1H, C -Ar-H,
25
3
4
6
ο
4
3,4
Et SnL [14]: Yield: 60%, yellow green solid; M.p.: 154–159 C,
J
= 2.48 Hz), 7.70–7.68 (dd, 1H, C ꢀ -Ar-H,
J
H,H
= 1.6, 8.16 Hz),
2
H,H
2
Conductivity: (ohm 1 cm2 mol ) in DMF: 13, FT-IR (v, cm ):
−
−1
−1
4
7.50–7.49 (d, 1H, C ꢀ -Ar-H,
J
= 1.36 Hz), 7.32–7.31 (d, 1H, C -
6
H,H
4
1
Ar-H, 4JH,H = 2.44 Hz), 7.00–6.98 (d, 1H, C ꢀ -Ar-H,
3
1
595 (C = N, m), 420 (Sn-N), 693 (Sn-O). H NMR [400 MHz,
J
= 8.2 Hz),
3
H,H
CDCl , δ(ppm)]: 8.47 (s, 1H, -N
=
C–H), 7.67–7.64 (dd, 1H,
6.04 (s, 2H, -CH ), 1.32–1.29 (t, 6H, -CH ), 0.80–0.78 (q, 4H, -
2 3
3
C ꢀ -Ar-H, 3,4JH,H
=
1.48, 8.12 Hz), 7.57–7.58 (d, 1H, C2ꢀ -Ar-H,
CH , 3JH,H = 8.33 Hz). C NMR [100 MHz, CDCl . δ(ppm)]: 176.17
13
6
2
3
4
JH,H = 1.4 Hz), 7.01–6.98 (d, 1H, C -Ar-H, 3JH,H = 8.92 Hz), 6.87–
6
(HO–C = N), 174.69 (HC=N), 169.18 (C -Br), 157.28 (C–OH),141.28
3
3
6
.85 (d, 1H, C ꢀ -Ar-H,
J
= 8.16 Hz), 6.43–6.42 (dd, 1H, C -Ar-H,
(C ), 139.96 (C ), 134.22 (C ), 131.33 (C ꢀ ), 129.56 (C ꢀ ), 125.00
5
H,H
5
6
4
1
1
6
3
,4
119
JH,H = 2.36, 8.92 Hz), 6.07 (s, 1H, -CH ), 6.02–6.01 (d, 1H, C -Ar-
(C ꢀ, 4ꢀ ), 120.39 (C ꢀ ꢀ ), 45.18 (-CH ), 49.31 (Et-C), 9.04 (Et-C).
Sn
2
3
2
3
2 , 5
H, 4
J
= 2.24 Hz), 2.97–2.95 (q, 4H,
3
J
= 14.12 Hz), 1.20–1.18
H,H
13
+
H,H
H,H
NMR [149.21 MHz, CDCl , δ(ppm)]: −162. MS: m/z (M ) Cacld. for
3
3
3
+
(t, 6H, -CH ,
J
= 7.04 Hz), 1.09–1.07 (t, 6H,
H,H
J
= 7.32 Hz),
C
H
19 18
Br N O Sn: 616.87; found: 617.88 (M + H) .
3
H,H
2
2
4
4
3
ο
0
.87–0.85 (q, 4H, Me,
J
= 8.31 Hz).
C NMR [100 MHz,
Bu SnL [19]: Yield: 69%, yellow solid; M.p.: 165–167 C, Con-
2
ductivity: (ohm 1 cm2 mol ) in DMF: 13.73, FT-IR (v, cm ):
−
−1
−1
CDCl , δ(ppm)]: 167.27 (HO–C = N), 163.35 (HC=N), 148.34 (C–OH),
3
1
1
46.50 (C ), 142.19 (C ), 140.96 (C ), 135.68(C ꢀ ), 129.79 (C ꢀ ),
1651 (C = N, m), 462 (Sn-N), 646 (Sn-O). H NMR [400 MHz,
4
6
1
1
6
1
26.90 (C3ꢀ, 4ꢀ ), 122.47 (C ), 120.57 (C ꢀ ), 115.79 (C ꢀ ), 112.06 (C ),
7.08 (-CH ), 24.90 (N-Et-C), 70.68 (N-Et-C), 42.16 (Et-C), 9.57 (Et-
CDCl , δ(ppm)]: 8.67 (s, 1H, -N = C–H), 7.78–7.77 (d, 1H, C -
5
2
5
3
3
6
Ar-H, 4
J
= 2.48 Hz), 7.72–7.70 (dd, 1H, C ꢀ -Ar-H,
3,4
J
H,H
= 1.6,
4
2
H,H
2
C). 119 Sn NMR [149.21 MHz, CDCl , δ(ppm)]: −152.12. MS: m/z
4
3
8.16 Hz), 7.64–7.63 (d, 1H, C ꢀ -Ar-H,
J
H,H
= 1.36 Hz), 7.40–7.39
6
+
+
4
(
M ) Cacld. for C
3
H
N O Sn: 530.20; found: 531.21 (M + H) .
(d, 1H, C -Ar-H, JH,H = 2.44 Hz), 6.87–6.86 (d, 1H, C ꢀ -Ar-H,
2
3
29
3
4
4
3
3JH,H = 8.2 Hz), 6.02 (s, 2H, -CH ), 1.72–1.69 (m, 8H, -CH ), 1.54–
H,H
Bu SnL [15]: Yield: 70%, yellow green solid; M.p.: 163–
2
2
2
13
ο
−1
cm2 mol ) in DMF: 14.01, FT-IR
−1
1.50 (t, 6H, Bu-H), 0.89 - 0.87 (t, 4H, 3
1
67 C, Conductivity: (ohm
J
= 7.32 Hz). C NMR
−
(
v, cm 1): 1685 (C = N, m), 418 (Sn-N), 667 (Sn-O). 1H NMR
[100 MHz, CDCl , δ(ppm)]: 178.86 (HO–C = N), 174.05 (HC=N),
3
[
400 MHz, CDCl , δ(ppm)]: 8.49 (s, 1H, -N = C–H), 7.64–7.62 (dd,
169.95 (C -Br), 160.48 (C–OH),150.14 (C ), 143.05 (C ), 139.39 (C ),
3
3
6
4
1
3
,4
1
4J
H, C ꢀ -Ar-H,
J
= 1.56, 8.18 Hz), 7.54–7.53 (d, 1H, C ꢀ -Ar-H,
131.52 (C ꢀ ), 128.50 (C ꢀ ), 125.85 (C3ꢀ, 4ꢀ ), 120.18 (C ꢀ ꢀ ), 45.67 (-
6
H,H
2
1 6 2 , 5
3
= 1.44 Hz), 6.98–6.96 (d, 1H, C -Ar-H,
J
= 8.92 Hz), 6.85–
119
H,H
6
H,H
CH ), 56.34 (Bu-C), 44.49 (Bu-C), 34.62 (Bu-C), 8.59 (Bu-C).
Sn
2
3
6
3
.83 (d, 1H, C ꢀ -Ar-H,
,4
J
= 8.2 Hz), 6.17–6.14 (dd, 1H, C -Ar-H,
+
5
H,H
5
NMR [149.21 MHz, CDCl3, δ(ppm)]: −267.08. MS: m/z (M ) Cacld.
JH,H = 2.4, 8.9 Hz), 6.01 (s, 2H, -CH ), 5.98–5.97 (d, 1H, C - Ar-H,
+
2
3
for C
H
Br N O Sn: 672.98; found: 673.98 (M + H) .
2
3
26
2
2
4
4JH,H = 2.32 Hz), 1.51–1.45 (m, 8H), 1.23–1.19 (m, 10H), 0.89 - 0.86
4
ο
Ph SnL [20]: Yield: 72%, Yellow solid; M.p.: 165–167 C, Con-
2
m, 10H). 13C NMR [100 MHz, CDCl , δ(ppm)]: 164.38 (HO–C = N),
(
ductivity: (ohm cm2 mol ) in DMF: 13.88, FT-IR (v, cm ): 1658
−1
−1
−1
3
1
61.24 (HC=N), 144.56 (C–OH), 141.89 (C ), 139.06 (C ), 137.36 (C ),
(C = N, m), 528 (Sn-N), 635 (Sn-O). 1H NMR [400 MHz, CDCl3,
4
6
1
1
34.78(C ꢀ ), 130.67 (C ꢀ ), 126.40 (C ꢀ ꢀ ), 123.67 (C ), 119.04 (C ꢀ ),
1 6 3 , 4 2
5
δ(ppm)]: 8.61 (s, 1H, -N = C–H), 7.93–7.90 (m, 5H, Sn-Ar-H), 7.89–
1
15.68 (C 5ꢀ ), 111.79 (C ), 45.08 (-CH ), 26.90 (N-Et-C), 72.05 (N-Et-
C), 44.88 (Bu-C), 32.78 (Bu-C), 9.05 (Bu-C).
7.88 (d, 1H, C6-Ar-H, 4JH,H = 1.64 Hz), 7.83–7.82 (d, 1H, C ꢀ -Ar-
3
2
2
119
Sn NMR [149.21 MHz,
H, 4JH,H = 2.48 Hz), 7.74–7.73 (d, 1H, C -Ar-H,
4
J
= 1.56 Hz),
4
H,H
+
CDCl , δ(ppm)]: −214.44. MS: m/z (M ) Cacld. for C27H N O Sn:
3
37
3
4
7.47–7.45 (m, 5H, Sn-Ar-H), 7.00 (s, 1H, C ꢀ -Ar-H), 6.95–6.93 (d, 1H,
6
+
5
86.31; found: 587.32 (M + H) .
3
13
C3ꢀ -Ar-H, JH,H = 8.16 Hz), 6.09 (s, 2H, -CH ). C NMR [100 MHz,
2
3
Ph SnL [16]: Yield: 68%, yellow green solid; M.p.: 150–
2
CDCl . δ(ppm)]: 175.73 (HO–C = N), 174.12 (HC=N), 170.40 (C -
3
3
ο
−1
cm2 mol ) in DMF: 13.70, FT-IR
−1
1
56 C, Conductivity: (ohm
Br), 156.18 (C–OH),150.30 (C ), 146.39 (C ), 142.19 (C ), 136.79
6
4
1
(
v, cm 1): 1595 (C = N, m), 479 (Sn-N), 700 (Sn-O). H NMR
−
1
(
(
C ꢀ ), 131.29 (C ꢀ ), 128.30 (C3ꢀ, 4ꢀ ), 126.01–117.29 (Sn-pHPh), 113.42
1 6
[
400 MHz, CDCl , δ(ppm)]: 8.54 (s, 1H, -N = C–H), 7.78–7.76 (dd,
119
3
C ꢀ ꢀ ), 46.82 (-CH ).
Sn NMR [149.21 MHz, CDCl , δ(ppm)]:
3
2
3
,4
2 , 5
1
4J
H, C ꢀ -Ar-H,
H,H
J
= 1.67, 8.07 Hz), 7.64–7.63 (d, 1H, C ꢀ -Ar-H,
+
6
H,H
2
−332.63. MS: m/z (M ) Cacld. for C27H18 Br N O Sn: 712.96; found:
2
2
4
= 3.56 Hz), 7.47 - 7.43 (m, 10H, Sn-Ar) 6.97–6.95 (d, 1H, C -
+
6
7
13.98 (M + H) .
Ar-H, 3
J
= 8.92 Hz), 6.87–6.84 (d, 1H, C ꢀ -Ar-H,
3
J
H,H
= 8.2 Hz),
H,H
5
3
,4
6
.12–6.10 (dd, 1H, C -Ar-H,
J
= 2.4, 8.9 Hz), 6.03 (s, 2H,
5
H,H
4 13
-
CH ), 5.98–5.97 (d, 1H, C - Ar-H,
J
H,H
= 2.32 Hz).
C NMR
2.6. Pharmacology
2
3
[
100 MHz, CDCl . δ(ppm)]: 168.46 (HO–C = N), 163.89 (HC=N),
3
1
50.58 (C–OH), 146.37 (C ), 140.47 (C ), 139.36 (C ), 135.93(C ꢀ ),
2.6.1. Cytotoxicity assay
4
6
1
1
1
31.59 (C ꢀ ), 128.29 (C3ꢀ, 4ꢀ ), 124.13–119.05 (Sn-Ph), 115.96 (C ),
The cytotoxicity of the synthesized compounds was evaluated
by in vitro assay as described by Mosmann(1983) with slight mod-
ifications [41]. The cytotoxicity was tested against a panel of three
different human carcinoma cell lines: A549 derived from human
alveolar adenocarcinoma epithelial cells (ATCC No.CCL-185); HeLa
derived from human cervical adenocarcinoma epithelial cells (ATCC
No. CCL-2); MCF7 derived from human breast adenocarcinoma ep-
ithelial cells (ATCC No. HTB-22) as well as normal cell line L6 de-
rived from rat skeletal muscle myoblast cells (ATCC No. CRL-1458).
6
5
1
11.27 (C ꢀ ), 106.03 (C ꢀ ), 103.05 (C ), 45.08 (-CH ), 26.90 (N-
2 5
119
3
2
Et-C), 72.05 (N-Et-C).
Sn NMR [149.21 MHz, CDCl , δ(ppm)]:
3
+
313.65. MS: m/z (M ) Cacld. for C31H29N O Sn: 626.28; found:
3 4
−
+
6
27.28 (M + H) .
4
ο
Me SnL [17]: Yield: 73%, yellow solid; M.p.: 157–163 C, Con-
2
ductivity: (ohm 1 cm2 mol ) in DMF: 14.85, FT-IR (v, cm ):
−
−1
−1
1
1
647 (C = N, m), 441 (Sn-N), 671 (Sn-O). H NMR [400 MHz,
CDCl , δ(ppm)]: 8.62 (s, 1H, -N = C–H), 7.74–7.73 (d, 1H, C -Ar-H,
3
6
4

J. Devi, J. Yadav, K. Lal et al.
Journal of Molecular Structure 1232 (2021) 129992
less than 16 ohm 1 cm2 mol which describes non electrolytic na-
ture. The compounds were soluble in the DMSO, methanol, CHCl3,
DMF but insoluble in water. Thermal analysis data suggested that
the compounds are non-volatile in nature and stable upto 160 °C.
−
−1
All the cells were cultured in Dulbecco’s Modified Eagle’s medium
supplemented with 10% Foetal bovine serum (FBS), 10% Penstrep
6
and 1% gentamicin. In brief, cells (1 × 10 per mL) were seeded
in tissue culture grade multiwell plates in complete medium, fol-
lowed by incubation under standard conditions in 37 °C humid-
ified 5% CO2 atmosphere. After 24 h, the complete medium was
replaced with FBS free medium and incubated overnight. Further,
the cells were treated with the samples in different concentra-
tions (1 to 160 μg/ml) into each well and incubated for 24 h.
Well containing medium alone (untreated cells) served as a con-
trol. On completion of incubation period, 10 μL of MTT (5 mg/mL)
was added to each well, mixed gently and again incubated for 4 h.
After the incubation period, cells were viewed under an inverted
microscope for the presence of dark purple crystals of formazan at
the bottom of the wells. Isopropanol (100 μL) with 0.04 N HCl was
added to each well and mixed thoroughly by repeated pipetting
with a multichannel pipette. The role of HCl is to convert phe-
nol red present in tissue culture medium to a yellow color that
does not interfere with the MTT formazan measurement andthe
role of isopropanol is to dissolve the formazan crystals to give a
homogeneous blue solution suitable for absorbance measurement.
The absorbance was measured on an ELISA plate reader (Filter-
Max F3 Multi-Mode Microplate Readers, Molecular Devices) with a
test wavelength of 570 nm and a reference wavelength of 630 nm.
All experiments were performed in triplicate and doxorubicin was
used as a standard drug (0.5 to 10 μg/ml). The effect of the syn-
thesized compounds on the proliferation of cells was expressed as
the% inhibition of cell proliferation and calculated as (Absorbance
of control cells - Absorbance of treated cells / Absorbance of con-
trol cells) × 100. Further, dose response curves were plotted to
find out the cytotoxic concentration (IC values) of the synthesized
3.2. Spectroscopic studies
FT-IR spectra
In the IR spectra, most manifested stretching vibration bands
for v-OH is present in the region 3475–3290 cm 1 in free lig-
ands which are absent in complexes indicated the coordination
of phenolic oxygen with the tin metal atom [44,45]. The diag-
nostic stretching absorption bands in Schiff base ligand appeared
−
at 3138–3094 cm 1 and 1689–1695 cm
−
−1
for v-N-H and v-C = O
which confirmed the existence of ligands in keto form [46]. The
non-appearance of above bands in complexes suggested that dur-
ing complexation ligands undergo tautomerization to enolic form
followed by deprotonation and coordination of oxygen to tin metal
center. Absorption bands at 1642–1616 cm 1 due to ν-C = N in lig-
ands gets shifted to lower value in the diorganotin(IV) complexes
indicating the coordination of azomethine nitrogen and shifting of
electron density to the tin metal from the nitrogen of azomethine
group [47].
−
Further, some additional bands appeared in the FT-IR spectra of
−1
the complexes due to Sn-N and Sn-O stretching at 528–408 cm
and 700–608 cm 1, respectively which confirm the coordination of
−
metal with the oxygen and nitrogen donor atoms [48].
1H. NMR spectra
In the NMR spectra, C –OH proton singlet appears in the range
2
5
0
of δ 13.53–11.11 ppm in ligands (1–4), which disappeared on com-
plexation showed the deprotonation and coordination of oxygen
with the tin metal. Another singlet at δ 12.33–8.87 ppm due to
N–H proton of ligands gets disappeared on complex formation, in-
dicated deprotonation and coordination of carbonyl oxygen with
the metal center [49,50]. The binding mode of the ligands was
also explained by azomethine proton (-CH = N) signal at δ 9.24–
8.31 ppm, gets shifted upfield on complexation and gives the tin
satellite peak with 3J(119 Sn- H) spin–spin coupling constant of 62–
65 Hz which indicates the release of electron from azomethine
nitrogen to tin atom and gives Sn-N coordinated bond [51]. The
aromatic protons and methylene protons in ligands resonated at δ
8.62–6.52 and δ 6.21–6.06 ppm, respectively which remains unal-
tered in diorganotin(IV) complexes.
compounds.
2
.6.2. Molecular docking
Docking studies were performed to analyze the binding mode of
compounds to their target structure using Molegro Virtual Docker (in-
stalled on an Intel Centrino Machine, Intel Corporation, Santa Clara,
CA, USA). Here, the docking studies were performed on potent cy-
2
3
1
totoxic active compounds 12 (Ph SnL ), 14 (Et SnL ) and moder-
2
2
4
ate cytotoxic compound 20 (Ph SnL ) against two different crystal
2
proteins Tyrosine kinase (PDB ID: 1T46) and EGFR kinase domain
(PDB ID: 2ITY). The 3D structures of the ligands were constructed
using Chem3D ultra8.0 software, and then minimize the energy by
MOPAC (semi-empirical quantum mechanics), Job Type with 100 in-
teractions and minimum RMS gradient of 0.01, and saved as protein
data bank (.pdb) format. The pre downloaded protein PDB structure
was imported in the workspace and the grid parameters were set as
X = 31.87, Y = 25.99, and Z = 35.09 (PDB ID: 1T46) and X = 30.25,
Y = 27.09, and Z = 34.04 (PDB ID: 2ITY) with a radius of approxi-
mately 15.00 A˚. The poses were examined manually and the best con-
formations were retained. The docking procedure was validated with
the comparison of the docked co-crystallized active ligand [42,43].
Some new signals appeared on complexation which confirms
the formation of organotin complexes. The methyl protons res-
onated at δ 0.91–0.89 ppm as a singlet with 2J(119 Sn- H) coupling
constants of 79 Hz [52]. The methylene proton of diethyl appeared
as quartet at δ 0.95–0.78 ppm with 3J( H– H) coupling constant
8.37–8.32 Hz. The methylene proton of dibutyl appeared as triplet
at δ 0.91–0.80 ppm with 3J( H– H) coupling constant at 7.32 Hz,
respectively. The diphenyltin protons in complexes appeared as
multiplet in the region δ 7.72–7.39 ppm.
1
1
1
1
1
3. Results and discussion
13C. NMR spectra
The 13C NMR spectra, azomethine carbon signal appeared at δ
3
.1. Synthetic aspect
1
68.74–170.04 ppm in the Schiff base ligands which gets shifted
The Schiff base ligands (H L1–4) (1–4) were synthesized by
downfield on the complex formation [53]. A signal at δ 146.05–
2
the condensation of piperonylic acid hydrazide and salicylalde-
hyde derivatives in methanol which were then reacted with di-
alkyl/diarylorganotin dichloride in tetrahydrofuran to get diorgan-
otin(IV) complexes (5–20) as represented in the Scheme 1. The
spectroscopic techniques and X-ray crystallographic study con-
cluded diorganotin(IV) complexes to show the pentacoordinated
geometry with the tridentate (NOO) Schiff base ligands. All the
compounds have sharp melting point, molar conductance value
150.02 ppm is due to C –OH carbon which shifted downfield
2
in complex formation. Some additional signals appeared in com-
plexes which are due to the metal-carbon bond formation at δ
9.06–8.45 ppm due to the metal - methyl (Sn-CH ) bond in the
3
dimethyltin complexes and signal at δ 10.14–9.78 ppm, δ 39.17–
41.03 ppm due to the metal-carbon bond in diethyltin complexes.
The carbon signal for the dibutyltin complexes were observed in
the range of δ 13.54–14.52 ppm and δ 26.72–34.13 ppm [54]. Some
5

J. Devi, J. Yadav, K. Lal et al.
Journal of Molecular Structure 1232 (2021) 129992
Scheme 1. Synthesis of Schiff bases (1–4) and their diorganotin(IV) complexes (5–20).
new signals in the aromatic range appeared at 130.16–127.62 ppm
assigned to the diphenyltin complexes.
ber of coordinated and lattice water in the complexes. The thermal
analysis of complexes were carried out in the range of 20 °C to
9
00 °C and common mass loss scheme is depicted at a particu-
1
19Sn. NMR
In the 119 Sn NMR spectra singlet appeared at δ −150.17 to
lar temperature range (Scheme 2). The thermal analysis curve of
2
the complex 9 (Me SnL ) is given in Fig. 2 and shows that the
2
−
157 ppm for methyl, δ −152.12 to −162 ppm for ethyl, δ −212.04
dimethyltin(IV) complex decompose in three step with first step of
to −267.08 ppm for butyl, δ −313.65 to –334.78 ppm for phenyl
complexes, respectively [55]. The range of chemical shifts indicated
the pentacoordinated geometry around the tin metal.
decomposition at 160 −288 °C with a weight loss of 6.67% (calcd.
6
.3%) which was due to the loss of methyl group directly attached
to the tin metal center and confirms the absence of lattice water
molecule in the complex. In second step the mass loss of 73.77%
Mass spectra
ο
(
calcd. 73.76%) at 288–456 C was due to loss of ligand moiety in
The molecular ion peak of all the synthesized compounds are
in close agreement with the expected molecular weight. The mass
spectra of H L2 ligand (2) which has molecular ion peak (par-
the complex and in third step the mass loss was 19.56% , which
was assigned of the complete decomposition of the complex, leav-
2
ο
ing SnO2 as end product at the temperature above 456 C. Other
+
ent peak) at m/z 330.3367 for [M + H] ion is closer to its ex-
complexes have same pattern of decomposition as described above.
The results of decomposition showed that percentage mass loss is
in good agreement with the theoretical value. From the TGA curve
it was concluded that the complexes are stable upto 160 °C which
confirms their non-volatile nature.
pected molecular weight. The mass spectra of diphenyltin com-
2
plex, [Ph SnL ] (12) shows molecular ion peak at m/z 601.0370
2
+
due to [M
+
H] ion and cationic radical molecular peaks
at m/z = 600.0363 and m/z = 600.0039. The mass peak at
m/z = 450.2309 is due to removal of two phenyl ring from the
complex (Fig. 1).
3
.3. X-Ray crystallography
Thermogravimetric analysis
Thermal studies of the compounds were carried out to know
about the volatile or non-volatile nature of compounds and num-
To further strengthen the coordination mode of ligand to tin
metal and to establish geometry of complexes, we have grown
6

J. Devi, J. Yadav, K. Lal et al.
Journal of Molecular Structure 1232 (2021) 129992
Fig. 1. HRMS of compounds: a H2L2 (2) and b. Ph2SnL2 (12) c. Ph2SnL2 (12) (Expanded form).
2
single crystal of compound 9 (Me SnL ). Single crystal was ob-
(SnO2NC2) coordinating with two oxygen and one nitrogen atom
of ligand molecule along with two terminal methyl groups (Fig. 3).
Two oxygen atoms (O1 and O4) are present in the axial posi-
tion of the TBP geometry. Metal-oxygen distances are ranging from
2.105(3) to 2.122(3) with the average distance of 2.114(3). Metal-
carbon distance is the shortest distance with the average value
2
tained over a month in DMSO at room temperature. It crystallizes
in monoclinic crystal system with the space group P2 /n (Table 1).
1
The asymmetric unit contains one crystallographically independent
tin metal, ligand molecule and two methyl groups. Crystal struc-
ture shows that tin has distorted trigonal bipyramidal geometry
7

J. Devi, J. Yadav, K. Lal et al.
Journal of Molecular Structure 1232 (2021) 129992
Table 1
2
Single crystal data and structure refinement parameters for compound 9 (Me2SnL ).
Structural parameter
9
Empirical formula
Formula weight
Crystal system
SnC17H15N3O6
476.01
Monoclinic
P21/n
Space group
a ( A˚ )
7.4314(2)
11.0389(3)
22.2417(7)
94.6450(10)
1818.59(9)
4
b ( A˚ )
c ( A˚ )
β (°)
V ( A˚ 3
)
Z
T/K
Crystal size/mm3
296
0.20 × 0.10 × 0.08
−
1.739 g/cm
3
Density (ρ)
−
1
Absorption Coefficient (μ)
Radiation (λ,Mo Kα)
θ range for data collection
Completeness to θ
1.445mm
0.71073A˚
2.60 to 26.00°
99.7%
Reflection Collected
23,982
Independent Reflections
Data/ Restraints/ Parameters
Refinement method
3569 (Rint= 0.0468)
3575/ 0/ 246
Full-matrix least-squares on F2
1.107
Goodness of Fit on F2
Final R indeces [ I > 2σ (I)]
R1 = 0.0331
wR2 = 0.0857
R1 = 0.0510
R indece s (all data)
wR2 = 0.0926
Table 3
Selected bond angles ( ° ) of complex 9.
C(8)-Sn(1)-C(9)
129.6(2)
O(1)-Sn(1)-N(2)
82.44(12)
C(8)-Sn(1)-O(1)
C(9)-Sn(1)-O(1)
C(8)-Sn(1)-O(4)
C(9)-Sn(1)-O(4)
O(1)-Sn(1)-O(4)
C(8)-Sn(1)-N(2)
C(9)-Sn(1)-N(2)
94.26(19)
94.93(19)
95.13(19)
96.76(19)
155.07(11)
117.07(16)
113.28(19)
O(4)-Sn(1)-N(2)
C(1)-O(1)-Sn(1)
C(7)-N(2)-N(3)
C(7)-N(2)-Sn(1)
N(3)-N(2)-Sn(1)
C(10)-O(4)-Sn(1)
C(10)-N(3)-N(2)
72.72(11)
134.7(3)
115.6(3)
128.6(3)
115.8(2)
115.3(2)
111.1(3)
2
Scheme 2. Proposed thermal decomposition mechanism of complex 9 (Me2SnL ).
Table 4
Important hydrogen bond interactions observed in SnC17 H15 N3O6.
D–H•••A
D–H ( A˚ )
H•••A ( A˚ )
D•••A ( A˚ )
D–H•••A (°)
#
1
C(16) – H(14)•••O(1)
C(17) – H(15)•••N(3)
0.93
0.93
2.59
2.51
3.488(7)
2.820(6)
164(1)
100(1)
Symmetry generated equivalent point is as follows, #1: x , −1 + y,z.
interactions are mainly observed for intramolecular stabilization
whereas C–H•••O interactions are observed for supramolecular
2
Fig. 2. Thermal decomposition curve of compound 9 (Me2SnL ).
stabilizations (Fig. 4). In the packing structure, one can find the 2
1
screw-axis is extended along the crystallographic b-axis. Although,
weak C–H•••N and C–H•••O interactions are responsible for the
three-dimensional packing, there are few electrophilic and electro-
phobic groups are free for hydrogen bonding interactions which
can provide biological activity.
Table 2
Selected Bond lengths ( A˚ ) of complex 9.
Sn(1)-C(8)
2.087(4)
O(2)-N(1)
1.224(5)
Sn(1)-C(9)
Sn(1)-O(1)
Sn(1)-O(4)
Sn(1)-N(2)
O(1)-C(1)
2.096(5)
2.105(3)
2.122(3)
2.185(3)
1.282(5)
N(2)-C(7)
N(2)-N(3)
O(4)-C(10)
N(3)-C(10)
1.278(5)
1.399(4)
1.282(5)
1.298(5)
2
2
R1 =ꢀ | FO| - | FC ||/ꢀ | FO |; wR2 = {ꢀ [w (FO - FC )]/ ꢀ [w
2
2
]} . w = 1/[ρ (F ) + (aP) + bP]. P = (FO ) + 2 (FC2)/3 for
1/2
2
2
2
2
(FO
)
O
1, a = 0.0498 and b = 0.6285.
3
.2. Cytotoxicity activity
˚
of 2.091(5) A among all other metal-coordination bonds. Metal–
˚
nitrogen bond length is 2.185(3) A. All the bond distances and bond
All the newly synthesized compounds (1–20) were tested for
angles (Table 2 and 3) are comparable with earlier reported tin
compounds. The molecular structure is stabilized by non-classical
hydrogen-bonding interactions. Here, the hydrogen donor atom
is carbon and acceptors are N and O atoms (Table 4). C–H•••N
their growth inhibitory activities against three cancer cell lines;
human lung carcinoma (A549), human cervical carcinoma (HeLa),
human breast carcinoma (MCF7) and one normal cell line; Rat my-
oblast cell Line (L6) by the MTT assay method. Doxorubicin is used
8

J. Devi, J. Yadav, K. Lal et al.
Journal of Molecular Structure 1232 (2021) 129992
2
Fig. 3. Ortep diagram of the compound 9(Me2SnL ).
2
Fig. 4. Hydrogen bonded supramolecular packing diagram of the compound 9 (Me2SnL ) (Green dotted lines correspond to the observed hydrogen boning interactions).
as a standard drug and in vitro cytotoxic activity of the synthesized
compounds is summarized in Table 5 and Fig. 6.
IC50 values of 31–34 μM, 27–31 μM and 22–32 μM against A549,
HeLa and MCF-7 cell lines, respectively; whereas toward normal
cell line (L6) the IC50 value is 35–46 μM (Table S3). Compound
Values are means of triplicate ± SD; Means not sharing a com-
mon letter within each row were significantly different at p < 0.05
1
2
3
8 (Ph SnL ), 9 (Me SnL ) and 13 (Me SnL ) gives potent cytotoxic
2
2
2
From the cytotoxic activity data of the Schiff base ligands, com-
activity against A549, HeLa and MCF-7 cell lines with IC50 values
are 37–49 μM, 37–45 μM and 44–60 μM. Good activity was also
shown by compounds 10, 16 and 17 with IC50 < 70 μM, while
moderate activity was shown by compounds 7, 11, 15, 18 and 20.
As compared with the standard drug, the cytotoxic potential of
4
pound 4 (H L ) is found to be good active against all cancer cell
2
lines having IC50 values 79, 79 and 89 μM for A549, HeLa and
1
2
MCF-7 cell lines, respectively. Compound 1 (H L ) and 2 (H L )
2
2
3
shows moderate activity and compound 3 (H L ) is least active
2
with IC50 values 229 μM, 222 μM and 208 μM against A549, HeLa
and MCF-7 cell lines.
all compounds (1–20) against normal cell line (L6) was less toxic.
1
Compound 6 (Et SnL ) induced least toxicity which is 57 times
2
2
On complexation, cytotoxic activity increases as compared with
less as compared to the standard drug. Compound 12 (Ph SnL ),
2
2
3
3
4
the free Schiff base ligands. Compound 12 (Ph SnL ), 14 (Et SnL )
14 (Et SnL ) and 19 (Bu SnL ) are excellently active against can-
2 2
2
2
4
and 19 (Bu SnL ) displayed excellently good cytotoxic activity with
cer cell lines and its toxicity against normal cell line is 7–8 times
2
9

J. Devi, J. Yadav, K. Lal et al.
Journal of Molecular Structure 1232 (2021) 129992
Table 5
IC50 values (μM) of compounds (1–20) against different cancer cell lines.
Cytotoxicity (IC50 μM)
S. No.
Compounds
A549
HeLa
MCF7
L6
1
2
3
4
5
6
7
8
9
H2L1
H2L2
H2L3
H2L4
Me2SnL1
Et2SnL1
Bu2SnL1
110 ± 32
121 ± 18
229 ± 14
79 ± 19
138 ± 18
191 ± 10
85 ± 19
39 ± 18
49 ± 10
58 ± 18
78 ± 9
104 ± 14
114 ± 15
222 ± 20
79 ± 14
143 ± 21
192 ± 17
77 ± 22
45 ± 11
44 ± 5
91 ± 43
128 ± 26
208 ± 56
89 ± 26
182 ± 36
197 ± 38
54 ± 23
44 ± 16
60 ± 14
45 ± 7
123 ± 52
128 ± 30
243 ± 45
155 ± 34
219 ± 34
286 ± 27
81 ± 14
70 ± 16
68 ± 6
2
Fig. 5. Molecular diagram compound 9 (Me2SnL ).
Ph2SnL1
Me2SnL2
Et2SnL2
Bu2SnL2
Ph2SnL2
Me2SnL3
Et2SnL3
1
1
1
1
1
0
1
2
3
4
59 ± 13
73 ± 18
27 ± 7
72 ± 21
95 ± 15
40 ± 7
62 ± 15
32 ± 13
46 ± 4
less as compared to the standard drug. Whereas compounds 1, 2,
31 ± 8
3
, 4, 5 and 18 are, nearly 20–40 times less toxic than doxorubicin
37 ± 7
37 ± 13
31 ± 6
46 ± 17
35 ± 4
in normal cells (Table 5 and Fig. 7).
34 ± 11
78 ± 22
68 ± 7
28 ± 13
84 ± 25
59 ± 8
3
The following SAR is concluded from the cytotoxic data:-
All the synthesized ligands and coordination compounds were
found to be active against tested cancer cell lines and compounds
15
16
Bu SnL
71 ± 12
69 ± 7
88 ± 20
63 ± 15
71 ± 18
106 ± 22
35 ± 6
2
Ph2SnL3
Me2SnL4
Et2SnL4
1
1
1
7
8
9
64 ± 23
111 ± 20
31 ± 1
64 ± 24
93 ± 15
29 ± 10
76 ± 26
3 ± 1
55 ± 16
65 ± 10
22 ± 11
69 ± 17
3 ± 0
2
3
4
1
2 (Ph SnL ), 14 (Et SnL ) and 19 (Bu SnL ) derived from ligands
Bu2SnL4
2
2
2
2
, 3 and 4 were most active compounds against A549, Hela and
20
21
Ph SnL4
79 ± 14
5 ± 0
97 ± 20
5 ± 1
2
MCF7 cell line where tin is coordinated with diphenyl, diethyl
and dibutyl groups, respectively. Further in these complexes ben-
zene ring is substituted with nitro, N,N’-diethylamino and dibromo
group, making these groups as most significant structural groups
for exhibiting cytotoxic activity apart from the backbone of the
Doxorubicin
A549- Human lung carcinoma cell line; HeLa - Human cervical carcinoma cell
line; MCF7- Human breast carcinoma cell line; L6- Rat myoblast cell Line (nor-
mal).
2
3
synthesized compound. However, ligands 2 (H L ), 3 (H L ) and 4
2
2
4
(
H L ) itself did not exhibit significant activity against tested can-
3.3. Docking study
2
cer cell lines, but its complexation with tin resulted in drastic in-
1
crease in cytotoxic activity. Ligand 1 (H L ) is moderately active
For tyrosine kinase and EGFR kinase domain
2
1
2
and its diphenyl complex 8 (Ph SnL ) is active against all the three
The promising cytotoxic activity of the compounds 12 (Ph SnL )
2
2
3
cancer cell lines. Poor activity of compounds 5, 6 and 18 indicates
and compound 14 (Et SnL ) against all the three tested cancer cell
2
the importance of substitution on benzene ring for cytotoxic activ-
ity.
lines (A549, HeLa and MCF7) prompted us to explore the pos-
sible binding interactions with the active site of tyrosine kinase
Fig. 6. Cytotoxic activities of Schiff bases and their organotin(IV) complexes showing their IC50 value against (a) Human lung carcinoma cell line (A549), (b) Human cervical
carcinoma cell line (Hela), (c) Human breast carcinoma cell line (MCF7) and (d) Normal Rat myoblast cell line (L6).
10

J. Devi, J. Yadav, K. Lal et al.
Journal of Molecular Structure 1232 (2021) 129992
Fig. 7. Key binding interactions of compound 12 with tyrosine kinase (PDB ID: 1T46). (H-bonds are depicted in dashed yellow lines).
Fig. 8. Key binding interactions of compound 14 with tyrosine kinase (PDB ID: 1T46). (H-bonds are depicted in dashed yellow lines).
Fig. 9. Key binding interactions of compound 20 with tyrosine kinase (PDB ID: 1T46). (H-bonds are depicted in dashed yellow lines).
and EGFR kinase domain by performing molecular docking simu-
cell division. This kinase has been found to correlate with a variety
of tumors such as breast cancer, lung cancer, colorectal cancer, etc.
and inhibition of tyrosine kinase has been shown to be a potential
therapeutic strategy for the treatment of cancer [56,57]. Therefore,
tyrosine kinase (TK) was chosen for the molecular docking studies
to support the observed in vitro cytotoxic activity and to add more
insight to predict the possible mechanism of action.
lations. Docking studies were also performed for moderate active
4
compound 20 (Ph SnL ) for comparison purpose. Tyrosine kinases,
2
essential for numerous cellular processes, catalyze phosphorylation
of various cellular substrates, which in turn regulates various cel-
lular functions when its activity become deregulated, it results in
alterations of phosphorylation process and leading to uncontrolled
11

J. Devi, J. Yadav, K. Lal et al.
Journal of Molecular Structure 1232 (2021) 129992
Fig. 10. Key binding interactions of compound 12 with EGFR kinase domain (PDB ID: 2ITY) (H-bonds are depicted in dashed yellow lines).
Fig. 11. Key binding interactions of compound 14 with EGFR kinase domain (PDB ID: 2ITY) (H-bonds are depicted in dashed yellow lines).
Fig. 12. Key binding interactions of compound 20 with EGFR kinase domain (PDB ID: 2ITY) (H-bonds are depicted in dashed yellow lines).
12

J. Devi, J. Yadav, K. Lal et al.
Journal of Molecular Structure 1232 (2021) 129992
The X-ray crystal structure of c-Kit tyrosine kinase and EGFR
kinase domain complexed with ligand was taken from RCSB Pro-
tein Data Bank (PDB code: 1T46 and 2ITY). All the poses generated
into the active site of 1T46 (c-Kit tyrosine kinase) and 2ITY (EGFR
kinase) were based on the scores. The docking scores of com-
compounds with the different target proteins resulted in the killing
of cancer cell.
Appendix A. Supplementary material
The crystallographic data for the compound can be found in
CCDC No: 1995315 by free of charge from The Cambridge Crystallo-
graphic Data Center (CCDC) via www.ccdc.cam.ac.uk/data_request/
cif.
2
3
pound 12 (Ph SnL ) and compound 14 (Et SnL ) were −8.8 and
2
2
−
8.7 Kcal/mol for tyrosine kinase and −8.1 and −8.3 Kcal/mol for
EGFR kinase domain, respectively. These compounds were found to
be almost equally active in vitro cytotoxic studies and their dock-
Declaration of Competing Interest
The authors declare no conflicts of interest.
Acknowledgement
ing scores are also almost equal. The docking score of compound
4
2
0 (Ph SnL ) was −8.0 Kcal/mol for both tyrosine kinase and EGFR
2
kinase domain, which is less than compound 12 and compound
4. This is also in line with the results of in vitro cytotoxic stud-
1
ies, where compound 20 was found to be less active than com-
pound 12 and 14. The pose with the highest total score was chosen
for analyzing the binding features which represented good binding
affinities between the c-Kit tyrosine kinase, epidermal growth fac-
tor receptor and the chosen compounds in terms of ionic, hydrogen
bond, aromatic and lipophilic interactions.
The author Jyoti Yadav thankful to APJ Abdul Kalam Central
instrumentation laboratory, and department of Chemistry, Guru
Jambheshwar University of Science & Technology, Hisar, India for
instrumentation and lab facility.
The docking results revealed that compounds show desired key
interactions in the active site of tyrosine kinase, where one of the
oxygen atom of 1,3-benzodioxole ring of compound 12 interacted
with the side chain of Arg791 via O…H-N strong hydrogen bonds
and N of diethyl amino group of compound 14 involved in hydro-
gen bond formation with the side chain of Tyr672. For 1T46 and
compound 20, each of the oxygen atoms involved in the complex
formation with tin interacted with the side chains of Ile789 and
Arg791 via strong O…H-N hydrogen bonds. In case of EGFR kinase
domain 2ITY, one of the oxygen atom of 1,3-benzodioxole ring in-
teracted with the side chains of Lys745 via O…H-N strong hydrogen
bond (compound 12), whereas the side chains of Glu762, Asp855
residues are involved in two hydrogen bonds formation with the
nitrogen of diethylamino group of compound 14. Whereas, hydro-
gen bond is formed via O…H-N between one of the oxygen atom
of 1,3-benzodioxole ring of compound 20 and side chain of the
Lys745 residue. Docking pose of tyrosine kinase and EGFR kinase
along with docked conformations of compound 12, 14 and 20 are
shown in Figs. 7–12. However, the docking score and interactions
shown by compounds in the ligand binding site of c-Kit tyrosine
kinase (PDB ID: 1T46) is much better as compared to the interac-
tions shown in the ligand binding site of EGFR kinase domain (PDB
ID: 2ITY), indicating the mechanism by which these compounds
exert cytotoxic effect is through the inhibition of c-Kit tyrosine ki-
nase.
Supplementary materials
Supplementary material associated with this article can be
found, in the online version, at doi:10.1016/j.molstruc.2021.129992.
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